1. 1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis.
- Author
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Nesterova G, Malicdan MC, Yasuda K, Sakaki T, Vilboux T, Ciccone C, Horst R, Huang Y, Golas G, Introne W, Huizing M, Adams D, Boerkoel CF, Collins MT, and Gahl WA
- Subjects
- Adult, Calcium blood, Child, Family Health, Female, Humans, Hypercalciuria etiology, Hypercalciuria genetics, Hypercalciuria metabolism, Male, Nephrocalcinosis etiology, Nephrocalcinosis metabolism, Nephrolithiasis etiology, Nephrolithiasis metabolism, Pedigree, Phosphates blood, Primary Cell Culture, Steroid Hydroxylases deficiency, Vitamin D blood, Vitamin D3 24-Hydroxylase, Nephrocalcinosis genetics, Nephrolithiasis genetics, Steroid Hydroxylases genetics
- Abstract
Background and Objectives: Elevated serum vitamin D with hypercalciuria can result in nephrocalcinosis and nephrolithiasis. This study evaluated the cause of excess 1,25-dihydroxycholecalciferol (1α,25(OH)2D3) in the development of those disorders in two individuals., Design, Setting, Participants, & Measurements: Two patients with elevated vitamin D levels and nephrocalcinosis or nephrolithiasis were investigated at the National Institutes of Health (NIH) Clinical Center and the NIH Undiagnosed Diseases Program, by measuring calcium, phosphate, and vitamin D metabolites, and by performing CYP24A1 mutation analysis., Results: Both patients exhibited hypercalciuria, hypercalcemia, low parathyroid hormone, elevated vitamin D (1α,25(OH)2D3), normal 25-OHD3, decreased 24,25(OH)2D, and undetectable activity of 1,25(OH)2D-24-hydroxylase (CYP24A1), the enzyme that inactivates 1α,25(OH)2D3. Both patients had bi-allelic mutations in CYP24A1 leading to loss of function of this enzyme. On the basis of dbSNP data, the frequency of predicted deleterious bi-allelic CYP24A1 variants in the general population is estimated to be as high as 4%-20%., Conclusions: The results of this study show that 1,25(OH)2D-24-hydroxylase deficiency due to bi-allelic mutations in CYP24A1 causes elevated serum vitamin D, hypercalciuria, nephrocalcinosis, and renal stones.
- Published
- 2013
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